A Non-Linear Relation between Levels of Adult Hippocampal Neurogenesis and Expression of the Immature Neuron Marker Doublecortin

Stable Adult Hippocampal Neurogenesis in Cannabinoid Receptor CB2 Deficient Mice

International Journal of Molecular Sciences ◽

10.3390/ijms20153759 ◽

2019 ◽

Vol 20 (15) ◽

pp. 3759 ◽

Cited By ~ 1

Author(s):

Leonore Mensching ◽

Nevena Djogo ◽

Christina Keller ◽

Sebastian Rading ◽

Meliha Karsak

Keyword(s):

Adult Neurogenesis ◽

Cannabinoid Receptor ◽

Hippocampal Neurogenesis ◽

Neural Progenitors ◽

Adult Hippocampal Neurogenesis ◽

Double Positive ◽

Cannabinoid Receptor 2 ◽

Immature Neuron ◽

G Protein Coupled ◽

Deficient Mice

The G-protein coupled cannabinoid receptor 2 (CB2) has been implicated in the regulation of adult neurogenesis in the hippocampus. The contribution of CB2 towards basal levels of proliferation and the number of neural progenitors in the subgranular zone (SGZ) of the dentate gyrus, however, remain unclear. We stained hippocampal brain sections of 16- to 17-week-old wildtype and CB2-deficient mice, for neural progenitor and immature neuron markers doublecortin (DCX) and calretinin (CR) and for the proliferation marker Ki67 and quantified the number of positive cells in the SGZ. The quantification revealed that CB2 deficiency neither altered overall cell proliferation nor the size of the DCX+ or DCX and CR double-positive populations in the SGZ compared to control animals. The results indicate that CB2 might not contribute to basal levels of adult neurogenesis in four-month-old healthy mice. CB2 signaling might be more relevant in conditions where adult neurogenesis is dynamically regulated, such as neuroinflammation.

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Transcriptome dynamics of hippocampal neurogenesis in macaques across the lifespan and aged humans

10.21203/rs.3.rs-1015150/v1 ◽

2021 ◽

Author(s):

Xiaoqun Wang ◽

Wei Wang ◽

Mengdi Wang ◽

Meng Yang ◽

Bo Zeng ◽

...

Keyword(s):

Granule Cells ◽

Interaction Analysis ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Cellular Heterogeneity ◽

Molecular Characteristics ◽

Immature Neuron ◽

Proinflammatory Responses ◽

Adult Nscs ◽

Single Nucleus

Abstract Whether adult hippocampal neurogenesis (AHN) persists in adult and aged humans remains extensive debates1-8. Here, to provide a better understanding of AHN of primates, droplet-based single nucleus RNA sequencing (snRNA-seq) is used to investigate the cellular heterogeneity and molecular characteristics of the hippocampi in macaques across the lifespan and in aged humans. We pinpoint the dynamics of the neurogenic lineage, including adult neural stem cells (NSCs) and immature neurons, and the diversity of astrocytes and microglia. In the neurogenic lineage, the regulatory continuum from adult NSCs to immature and mature granule cells is investigated. We identify ETNPPL as a primate-specific NSC marker and verify STMN1 and STMN2 as immature neuron markers in primates. Importantly, we also illustrate a cluster of active astrocytes and microglia exhibiting proinflammatory responses in aged samples. The interaction analysis implies that astrocytes are more important niche cells that provide signals inducing the proliferation, quiescence and inflammation of adult NSCs at different stages and thus are attributed to the decrease and variability of AHN in adult and elderly.

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A non-linear relation between levels of adult hippocampal neurogenesis and expression of the immature neuron marker doublecortin

10.1101/2020.05.26.115873 ◽

2020 ◽

Cited By ~ 1

Author(s):

Indira Mendez-David ◽

Denis J David ◽

Claudine Deloménie ◽

Jean-Martin Beaulieu ◽

Alain M. Gardier ◽

...

Keyword(s):

Mouse Model ◽

Chronic Stress ◽

Granule Cells ◽

Antidepressant Treatment ◽

Hippocampal Neurogenesis ◽

Neural Progenitors ◽

Adult Hippocampal Neurogenesis ◽

List Type ◽

Stress Model ◽

Immature Neuron

ABSTRACTWe investigated the mechanisms underlying the effects of the antidepressant fluoxetine on behavior and adult hippocampal neurogenesis (AHN). After confirming our earlier report that the signaling molecule β2-arrestin is required for the antidepressant-like effects of fluoxetine, we found that the effects of fluoxetine on proliferation of neural progenitors and on survival of adult-born granule cells are absent in the β2-arrestin knockout (β2-Arr KO) mice. To our surprise fluoxetine induced a dramatic upregulation of doublecortin (DCX) in the β2-Arr KO mice, indicating that DCX expression can be increased even though AHN is not. We discovered two other conditions where DCX expression is regulated non linearly compared to levels of AHN: a chronic stress model where DCX is upregulated and an inflammation model where DCX is down regulated. We conclude that assessing DCX expression alone to quantify levels of AHN can be misleading and that caution should be applied when label retention techniques are not available.HIGHLIGHTSβ2-arrestin (β-Arr2) is required for the antidepressant-like effects of fluoxetine.A dramatic upregulation of doublecortin (DCX) is observed in the β2-Arr KO mice after antidepressant treatment whereas its effects on proliferation of neural progenitors and on survival of adult-born granule cells are absent.DCX is more upregulated than the number of young neurons in a mouse model of depression.DCX is more down regulated than the number of young neurons in a model of inflammation.microRNAs (miRs) may contribute to the regulation of DCX mRNA expression.

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Genetic Ablation of the Inducible Form of Nitric Oxide in Male Mice Disrupts Immature Neuron Survival in the Adult Dentate Gyrus

Frontiers in Immunology ◽

10.3389/fimmu.2021.782831 ◽

2021 ◽

Vol 12 ◽

Author(s):

Gabriel G. Fernandes ◽

Karla C. M. Costa ◽

Davi S. Scomparin ◽

Juliana B. Freire ◽

Francisco S. Guimarães ◽

...

Keyword(s):

Nitric Oxide ◽

Dentate Gyrus ◽

Hippocampal Formation ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Extrinsic Factors ◽

Double Labeling ◽

Genetic Ablation ◽

Neuron Survival ◽

Immature Neuron

Inducible nitric oxide synthase (iNOS) is an enzyme upregulated in the brain during neuroimmune stimuli which is associated with an oxidative and pro-inflammatory environment in several brain regions, including the hippocampal formation and the prefrontal cortex. The dentate gyrus of the hippocampal formation is the site of a process known as adult hippocampal neurogenesis (AHN). Although many endogenous and extrinsic factors can modulate AHN, the exact participation of specific proinflammatory mediators such as iNOS in these processes remains to be fully elucidated. Here, we investigated how the total genetic ablation of iNOS impacts the hippocampal neurogenic niche and microglial phenotype and if these changes are correlated to the behavioral alterations observed in iNOS knockout (K.O.) mice submitted or not to the chronic unpredictable stress model (CUS - 21 days protocol). Contrary to our initial hypothesis, at control conditions, iNOS K.O. mice displayed no abnormalities on microglial activation in the dentate gyrus. However, they did exhibit impaired newborn cells and immature neuron survival, which was not affected by CUS. The reduction of AHN in iNOS K.O. mice was accompanied by an increased positive coping response in the tail suspension test and facilitation of anxiety-like behaviors in the novelty suppressed feeding. Next, we investigated whether a pro-neurogenic stimulus would rescue the neurogenic capacity of iNOS K.O. mice by administering in control and CUS groups the antidepressant escitalopram (ESC). The chronic treatment with ESC could not rescue the neurogenic capacity or the behavioral changes observed in iNOS K.O. mice. Besides, in the ventromedial prefrontal (vmPFC) cortex there was no change in the expression or the chronic activation of PV neurons (evaluated by double labeling PV with FOSB) in the prelimbic (PrL) or infralimbic subregions. FOSB expression, however, increased in the PrL of iNOS K.O. mice. Our results suggest that iNOS seems essential for the survival of newborn cells and immature neurons in the hippocampus and seem to partially explain the anxiogenic-like behavior observed in iNOS K.O. mice. On the other hand, the iNOS ablation appears to result in increased activity of the PrL which could explain the antidepressant-like behaviors of iNOS K.O mice.

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